Glycoprotein IIb/IIIa complex mediates platelet aggregation by its ability to bind fibrinogen and has been implicated in regulation of platelet calcium influx. Platelets from individuals affected with Glanzmanns thrombasthenia lack the Iib/IIIa complex on their platelets and have decreased influx of calcium. Blocking of the Iib/IIIa complex on normal platelets with monoclonal antibodies or disrupting the complex by incubation with EDTA at 37 C also produces a decrease in calcium influx. Moreover, isolated Iib/IIIA complexes can act as calcium ion channels when they are reconstituted into lipid vesicles. We have studied the mechanism behind store-regulated calcium influx in platelets. Calcium stores appear to have the ability to increase plasma membrane permeability to calcium when these stores are depleted of their calcium. This initiates calcium influx into the cell which is stopped when stores are refilled. The regulatory mechanism behind this influx is not known. We have investigated whether Iib/IIIa complex mediates the store-regulated calcium influx across plasma membrane. The glycoprotein Iib/IIIa complex was disrupted by treatment with EDTA and warming at 37 C as previously reported or blocked with the peptide RGDS which prevents fibrinogen binding to Iib/IIIa. Such treatments did not have an effect on thapsigargin-induced calcium influx. Thapsigargin can deplete intracellular stores and mimick store-regulated calcium influx. Thus Iib/IIIa does not appear to be the calcium channel operated by internal calcium stores.